The Influence of Pituitary, Adrenal, and Parathyroid Hormones on Hemostasis and Thrombosis

Alessandro Squizzato; Bregje Van Zaane; Victor E.A Gerdes; Harry R Büller

doi:10.1055/s-0030-1270070

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2011; 37(1): 041-048
DOI: 10.1055/s-0030-1270070

The Influence of Pituitary, Adrenal, and Parathyroid Hormones on Hemostasis and Thrombosis

Alessandro Squizzato¹ ^, ² , Bregje Van Zaane² ^, ³ , Victor E.A Gerdes² ^, ³ , Harry R. Büller²

¹Research Center on Thromboembolic Disorders and Antithrombotic Therapies, Department of Clinical Medicine, University of Insubria, Varese, Italy
²Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
³Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands

Abstract

ABSTRACT

Endocrine disorders can influence the hemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. The present review updates the available evidence on the influence of pituitary, adrenal, and parathyroid hormones on the coagulation and the fibrinolytic system, and their possible clinical implications. The literature supports a possible relevant clinical effect of the imbalance between coagulation and fibrinolysis on thrombotic events in endogenous Cushing's syndrome. An effect on markers of coagulation and fibrinolysis has been shown for hyperprolactinemia, growth hormone excess or deficiency, exogenous hypercortisolism, pheochromocytoma, primary hyperaldosteronism, and hyperparathyroidism. However, the clinical relevance is still unproven. Until definitive evidence is available, clinicians should be aware of the possibility that endocrine disorders may be risk factors for thrombotic events.

KEYWORDS

Coagulation - hypercortisolism - prolactin - growth hormone - parathyroid - bleeding - thrombosis

Volltext

Referenzen

REFERENCES

1 Squizzato A, Gerdes V E, Ageno W, Büller H R. The coagulation system in endocrine disorders: a narrative review. Intern Emerg Med. 2007; 2 (2) 76-83
2 Franchini M, Lippi G, Manzato F, Vescovi P P, Targher G. Hemostatic abnormalities in endocrine and metabolic disorders. Eur J Endocrinol. 2010; 162 (3) 439-451
3 Atmaca A, Gurlek A, Dagdelen S et al.. Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times. Exp Clin Endocrinol Diabetes. 2006; 114 (4) 188-191
4 Wallaschofski H, Lohmann T, Hild E et al.. Enhanced platelet activation by prolactin in patients with ischemic stroke. Thromb Haemost. 2006; 96 (1) 38-44
5 Reuwer A Q, Nieuwland R, Fernandez I et al.. Prolactin does not affect human platelet aggregation or secretion. Thromb Haemost. 2009; 101 (6) 1119-1127
6 Erem C, Kocak M, Nuhoglu I, Yilmaz M, Ucuncu O. Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma. Clin Endocrinol (Oxf). 2009; December 18 (Epub ahead of print
7 Devin J K, Blevins Jr L S, Verity D K et al.. Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency. J Clin Endocrinol Metab. 2007; 92 (9) 3633-3639
8 Erem C, Nuhoglu I, Kocak M et al.. Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI. Endocrine. 2008; 33 (3) 270-276
9 Gómez J M, Sahún M, Vila R et al.. Peripheral fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf). 2006; 64 (6) 632-639
10 Gómez J M, Sahún M, Vila R et al.. Elevation of E-selectin concentrations may correlate with potential endothelial dysfunction in individuals with hypopituitarism during therapy with growth hormone. Curr Neurovasc Res. 2007; 4 (1) 55-62
11 Miljic D, Miljic P, Doknic M et al.. Changes in prothrombin and activated partial thromboplastin time during replacement therapy with human recombinant growth hormone in growth hormone deficient adults. Hormones (Athens). 2006; 5 (3) 187-191
12 Van Zaane B, Nur E, Squizzato A et al.. Hypercoagulable state in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab. 2009; 94 (8) 2743-2750
13 Erem C, Nuhoglu I, Yilmaz M et al.. Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest. 2009; 32 (2) 169-174
14 Kastelan D, Dusek T, Kraljevic I et al.. Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers. Endocrine. 2009; 36 (1) 70-74
15 Casonato A, Daidone V, Sartorello F et al.. Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome. Br J Haematol. 2008; 140 (2) 230-235
16 Baranyai R, Nonell A, Deuschle M, Lederbogen F. How depression may increase cardiac risk: effect of hypercortisolism on platelet activation markers: preliminary data. Neuropsychobiology. 2008; 57 (3) 146-150
17 Eggers A E. Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke. Med Hypotheses. 2006; 67 (5) 1065-1071
18 Erem C, Kocak M, Hacihasanoglu A, Yilmaz M, Saglam F, Ersoz H O. Blood coagulation, fibrinolysis and lipid profile in patients with primary hyperparathyroidism: increased plasma factor VII and X activities and D-Dimer levels. Exp Clin Endocrinol Diabetes. 2008; 116 (10) 619-624
19 Erem C, Kocak M, Nuhoglu I, Yilmaz M, Ucuncu O. Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism. Eur J Endocrinol. 2009; 160 (5) 863-868
20 Chertok-Shacham E, Ishay A, Lavi I, Luboshitzky R. Biomarkers of hypercoagulability and inflammation in primary hyperparathyroidism. Med Sci Monit. 2008; 14 628-632
21 Raaz D, Wallaschofski H, Stumpf C et al.. Increased prolactin in acute coronary syndromes as putative co-activator of ADP-stimulated P-selectin expression. Horm Metab Res. 2006; 38 (11) 767-772
22 Verhelst J, Abs R. Cardiovascular risk factors in hypopituitary GH-deficient adults. Eur J Endocrinol. 2009; 161 ((Suppl 1) S41-S49
23 Melmed S. Medical progress: acromegaly. N Engl J Med. 2006; 355 (24) 2558-2573
24 Newell-Price J, Bertagna X, Grossman A B, Nieman L K. Cushing's syndrome. Lancet. 2006; 367 (9522) 1605-1617
25 Dekkers O M, Biermasz N R, Pereira A M et al.. Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab. 2007; 92 (3) 976-981
26 Etxabe J, Vazquez J A. Morbidity and mortality in Cushing's disease: an epidemiological approach. Clin Endocrinol (Oxf). 1994; 40 (4) 479-484
27 Albiger N, Testa R M, Almoto B et al.. Patients with Cushing's syndrome have increased intimal media thickness at different vascular levels: comparison with a population matched for similar cardiovascular risk factors. Horm Metab Res. 2006; 38 (6) 405-410
28 Geerts W H, Bergqvist D, Pineo G F American College of Chest Physicians et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 ((6, Suppl)) 381S-453S
29 van Staa T P, Leufkens H G, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM. 2000; 93 (2) 105-111
30 Jilma B, Cvitko T, Winter-Fabry A, Petroczi K, Quehenberger P, Blann A D. High dose dexamethasone increases circulating P-selectin and von Willebrand factor levels in healthy men. Thromb Haemost. 2005; 94 (4) 797-801
31 Brotman D J, Girod J P, Posch A et al.. Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers. Thromb Res. 2006; 118 (2) 247-252
32 Darmon P, Dadoun F, Boullu-Ciocca S, Grino M, Alessi M C, Dutour A. Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity. Am J Physiol Endocrinol Metab. 2006; 291 (5) E995-E1002
33 Dover A R, Hadoke P W, Walker B R, Newby D E. Acute effects of glucocorticoids on endothelial fibrinolytic and vasodilator function in humans. J Cardiovasc Pharmacol. 2007; 50 (3) 321-326
34 Lewis G P, Piper P J. Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids. Nature. 1975; 254 (5498) 308-311
35 Moraes L A, Paul-Clark M J, Rickman A, Flower R J, Goulding N J, Perretti M. Ligand-specific glucocorticoid receptor activation in human platelets. Blood. 2005; 106 (13) 4167-4175
36 Souverein P C, Berard A, Van Staa T P et al.. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart. 2004; 90 (8) 859-865
37 Wei L, MacDonald T M, Walker B R. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med. 2004; 141 (10) 764-770
38 Calvo-Alén J, Toloza S M, Fernández M LUMINA Study Group et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheum. 2005; 52 (7) 2060-2068
39 Stolz E, Klötzsch C, Schlachetzki F, Rahimi A. High-dose corticosteroid treatment is associated with an increased risk of developing cerebral venous thrombosis. Eur Neurol. 2003; 49 (4) 247-248
40 Yale S H, Medlin S C, Liang H, Peters T, Glurich I, Mazza J J. Risk assessment model for venothromboembolism in post-hospitalized patients. Int Angiol. 2005; 24 (3) 250-254
41 Gaab M R, Trost H A, Alcantara A German Ultrahigh Dexamethasone Head Injury Study Group et al. “Ultrahigh” dexamethasone in acute brain injury. Results from a prospective randomized double-blind multicenter trial (GUDHIS). Zentralbl Neurochir. 1994; 55 (3) 135-143
42 Høgevold H E, Høiseth A, Reikerås O. Effect of high-dose corticosteroids on the incidence of deep vein thrombosis after total hip replacement. Arch Orthop Trauma Surg. 1991; 111 (1) 29-31
43 Sartori M T, Rigotti P, Marchini F et al.. Plasma fibrinolytic capacity in renal transplant recipients: effect of steroid-free immunosuppression therapy. Transplantation. 2003; 75 (7) 994-998
44 van de Wyngaert F A, Beguin C, D'Hooghe M B et al.. A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurol Belg. 2001; 101 (4) 210-216
45 Bottles K D, Morrissey J H. Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells. Blood Coagul Fibrinolysis. 1993; 4 (3) 405-414
46 Reddy K V, Bhattacharjee G, Schabbauer G et al.. Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability. J Leukoc Biol. 2004; 76 (1) 145-151
47 van Zonneveld A J, Curriden S A, Loskutoff D J. Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter. Proc Natl Acad Sci U S A. 1988; 85 (15) 5525-5529
48 Yamamoto Y, Ishizu A, Ikeda H, Otsuka N, Yoshiki T. Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells: an additive effect to tumor necrosis factor-alpha. Pathobiology. 2004; 71 (6) 295-301
49 Bergthorsdottir R, Leonsson-Zachrisson M, Odén A, Johannsson G. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab. 2006; 91 (12) 4849-4853
50 van den Akker E L, Koper J W, van Rossum E F et al.. Glucocorticoid receptor gene and risk of cardiovascular disease. Arch Intern Med. 2008; 168 (1) 33-39
51 Zhou W, Ding S F. Concurrent pheochromocytoma, ventricular tachycardia, left ventricular thrombus, and systemic embolization. Intern Med. 2009; 48 (12) 1015-1019
52 von Känel R, Dimsdale J E. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol. 2000; 65 (6) 357-369
53 Hoppener M R, Kraaijenhagen R A, Hutten B A, Büller H R, Peters R JG, Levi M. Beta-receptor blockade decreases elevated plasma levels of factor VIII:C in patients with deep vein thrombosis. J Thromb Haemost. 2004; 2 (8) 1316-1320
54 Shulkin B L, Shapiro B, Sisson J C. Pheochromocytoma, polycythemia, and venous thrombosis. Am J Med. 1987; 83 (4) 773-776
55 Grant P J. Hormonal regulation of the acute haemostatic response to stress. Blood Coagul Fibrinolysis. 1990; 1 (3) 299-306
56 Ganguly A. Primary aldosteronism. N Engl J Med. 1998; 339 (25) 1828-1834
57 Milliez P, Girerd X, Plouin P F, Blacher J, Safar M E, Mourad J J. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005; 45 (8) 1243-1248
58 Vaughan D E, Lazos S A, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis. J Clin Invest. 1995; 95 (3) 995-1001
59 Brown N J, Agirbasli M A, Williams G H, Litchfield W R, Vaughan D E. Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. Hypertension. 1998; 32 (6) 965-971
60 Oikawa T, Freeman M, Lo W, Vaughan D E, Fogo A. Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int. 1997; 51 (1) 164-172
61 Ducros E, Berthaut A, Mirshahi S S et al.. Aldosterone modifies hemostasis via upregulation of the protein-C receptor in human vascular endothelium. Biochem Biophys Res Commun. 2008; 373 (2) 192-196
62 Celi A, Del Fiorentino A, Cianchetti S, Pedrinelli R. Tissue factor modulation by angiotensin II: a clue to a better understanding of the cardiovascular effects of renin-angiotensin system blockade?. Endocr Metab Immune Disord Drug Targets. 2008; 8 (4) 308-313
63 Asselbergs F W, Williams S M, Hebert P R et al.. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels. Thromb Haemost. 2006; 96 (4) 471-477
64 Asselbergs F W, Williams S M, Hebert P R et al.. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels. Genomics. 2007; 89 (3) 362-369
65 Asselbergs F W, Williams S M, Hebert P R et al.. The effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels are dependent on environmental context. Hum Genet. 2007; 122 ((3-4)) 275-281
66 Fogari R, Zoppi A. Antihypertensive drugs and fibrinolytic function. Am J Hypertens. 2006; 19 (12) 1293-1299
67 Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ. 2006; 333 (7563) 330
68 Walker M D, Silverberg S J. Cardiovascular aspects of primary hyperparathyroidism. J Endocrinol Invest. 2008; 31 (10) 925-931
69 Hagström E, Hellman P, Larsson T E et al.. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009; 119 (21) 2765-2771
70 Walker M D, Fleischer J, Rundek T et al.. Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab. 2009; 94 (10) 3849-3856
71 Viganò G, Gotti E, Comberti E, Giangrande A, Trevisan R, Remuzzi G. Hyperparathyroidism does not influence the abnormal primary haemostasis in patients with chronic renal failure. Nephrol Dial Transplant. 1989; 4 (11) 971-974
72 Leithner C, Kovarik J, Sinzinger H, Woloszczuk W. Parathyroid hormone does not inhibit platelet aggregation. Lancet. 1984; 1 (8373) 367-368
73 Targher G, Pichiri I, Zoppini G, Bonora E, Chonchol M. Hemostatic and fibrinolytic abnormalities in endocrine diseases: a narrative review. Semin Thromb Hemost. 2009; 35 (7) 605-612
74 van Zaane B, Reuwer A Q, Büller H R, Kastelein J J, Gerdes V E, Twickler M T. Hormones and cardiovascular disease: a shift in paradigm with clinical consequences?. Semin Thromb Hemost. 2009; 35 (5) 478-487
75 Rosendaal F R. Venous thrombosis: a multicausal disease. Lancet. 1999; 353 (9159) 1167-1173

Alessandro SquizzatoM.D.

Medicina Interna 1, Ospedale di Circolo

viale Borri, 57, 21100 Varese, Italy

eMail: alexsquizzo@libero.it